Muscle functional MRI to evaluate quadriceps dysfunction in patellofemoral pain.

PURPOSE: A dysfunction of the quadriceps muscle group has often been suggested to play an important role in the pathophysiology of patellofemoral pain (PFP). However, consensus is lacking regarding the quadriceps recruitment pattern of patients with PFP. The aim of this study was to examine by muscle functional magnetic resonance imaging if patients with PFP actually exhibit an altered activation of the muscles that play a significant role in the dynamic balance of the patella. METHODS: Forty-six patients with PFP (25 female and 21 male, mean ± SD age = 25.0 ± 7.4 yr) and 30 healthy control subjects (17 female and 13 male, mean ± SD age = 21.6 ± 4.5 yr) underwent MRI of the quadriceps before and immediately after a squat exercise. The transverse relaxation time (T2) and the T2 shift were calculated for the vasti muscles. RESULTS: There were no significant differences in the T2 values at rest and the T2 shift values between the patient and the control groups, except for the T2 rest value of the VMVI of females (P = 0.007). The T2 shift of the VL was significantly smaller than the T2 shift of the VMVI in both study groups (male P < 0.001 and female P = 0.044), while in females, the T2 shift of the VMO was also significantly smaller than the T2 shift of the VMVI (P = 0.027). CONCLUSIONS: The activation pattern of the quadriceps is not altered in patients with PFP for both males and females. Because the relative contribution of the quadriceps muscles to a functional activity has not been modified, there is no evidence for quadriceps dysfunction.

What predicts functional outcome after treatment for patellofemoral pain?

PURPOSE: Although physical therapy is known to be effective in treating patellofemoral pain (PFP), there is considerable individual variation in the treatment response. It is unclear why some patients benefit from a specific treatment while others do not experience improvement. This study, using a prospective study design, aims to identify factors that could predict the short-term functional outcome and account for the variation frequently seen in the outcome after conservative treatment of PFP. METHODS: Thirty-six patients (20 female and 16 male with a mean age of 23.8 ± 6.7 yr) followed a physical therapy rehabilitation program of 7 wk. Before this treatment, all patients were evaluated on subjective symptoms (pain on visual analog scales in millimeters) and functional performance (step test expressed as highest level, single-legged hop test in centimeters, and triple-hop test in centimeters). The concentric and eccentric knee extensor strength at 60°.s(-1) and 240°.s(-1) (N.m) were measured as well as the quadriceps muscle size by calculating the cross-sectional area (cm(2)) with magnetic resonance imaging. The success of the treatment was evaluated by the functional Kujala anterior knee pain scale. A linear regression model was used to identify predisposing factors for the functional outcome. RESULTS: The total quadriceps cross-sectional area (P = 0.010), the eccentric average peak torque at 60°.s(-1) (P = 0.015), and the frequency of pain at baseline (P = 0.012) have been indicated as predisposing variables in the short-term functional outcome after a physical therapy rehabilitation program for PFP (adjusted R(2) = 0.46). CONCLUSION: Patients with a greater quadriceps muscle size, lower eccentric knee strength, and less pain have a better short-term functional outcome after conservative treatment for PFP.

Is hip muscle weakness a predisposing factor for patellofemoral pain in female novice runners? A prospective study.

BACKGROUND: Hip muscle weakness has been proposed to contribute to patellofemoral malalignment and the development of the patellofemoral dysfunction syndrome (PFDS). However, from the retrospective studies that have addressed this issue, it is still unclear if hip muscle weakness is a cause or a consequence of PFDS. PURPOSE: This study was undertaken to investigate if hip muscle weakness is a predisposing factor for the development of PFDS. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: Before the start of a 10-week "start to run" program, the isometric strength of the hip flexor, extensor, abductor, adductor, and external and internal rotator muscles was measured in 77 healthy female novice runners. During the 10-week training period, patellofemoral pain was diagnosed and registered by an orthopaedic surgeon. RESULTS: Statistical analysis revealed that there was no significant difference in strength of any of the assessed hip muscle groups between the runners who did and did not develop PFDS. Logistic regression analysis did not identify a deviation in strength of any of the assessed hip muscle groups as a risk factor for PFDS. CONCLUSION: The findings of this study suggest that isometric hip muscle strength might not be a predisposing factor for the development of PFDS.

Vastus medialis obliquus atrophy: does it exist in patellofemoral pain syndrome?

BACKGROUND: Quadriceps atrophy and in particular atrophy of the vastus medialis obliquus (VMO) muscle have been frequently related with patellofemoral pain syndrome (PFPS), despite very little objective evidence. HYPOTHESIS: Patients with PFPS exhibit atrophy of the VMO in comparison with healthy controls. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Forty-six patients with PFPS and 30 healthy control persons with similar age, gender, body mass index, and activity index distributions underwent magnetic resonance imaging (MRI) of the quadriceps. The muscle size was determined by calculating the cross-sectional area of the total quadriceps and its components. RESULTS: The cross-sectional area (CSA) of the VMO was significantly smaller in the PFPS group than in the control group (16.67 ± 4.97 cm(2) vs 18.36 ± 5.25 cm(2)) (P = .040). A tendency was noted for a smaller total quadriceps CSA for the PFPS patients at midthigh level (66.99 ± 15.06 cm(2) vs 70.83 ± 15.30 cm(2)) (P = .074). CONCLUSION: This is the first study to examine VMO size in PFPS patients by MRI. Patients with patellofemoral problems exhibited atrophy of the VMO. Although it is not clear whether this atrophy is a result or a cause of PFPS, the results of this study do show that atrophy of the VMO is a contributing factor in PFPS. Longitudinal, prospective studies are needed to establish the cause-effect relation of VMO atrophy and PFPS.

Does bracing influence brain activity during knee movement: an fMRI study.

Studies have shown that proprioceptive inputs during active and passive arm movements are processed in the primary and secondary somatosensory cortex and supplementary motor area of the brain. At which level of the central nervous system proprioceptive signals coming from the knee are regulated remains to be elucidated. In order to investigate whether there is a detectable difference in brain activity when various proprioceptive inputs are exerted at the knee, functional magnetic resonance imaging (fMRI) was used. fMRI in 13 healthy, right leg-dominant female volunteers compared brain activation during flexion-extension movements of the right knee under three different conditions: with application of a tight knee brace, with application of a moderate tight knee sleeve, and without application of a brace or sleeve. Brain activation was detected in the primary sensorimotor cortex (left and right paracentral lobule) and in the left superior parietal lobule of the brain. There was a significantly higher level of brain activation with the application of the brace and sleeve, respectively, compared to the condition without a brace or sleeve. A significantly higher cortical activation was also seen when comparing the braced condition with the condition when a sleeve was applied. The results suggest that peripheral proprioceptive input to the knee joint by means of a brace or sleeve seems to influence brain activity during knee movement. The results of this study also show that the intensity of brain activation during knee movement can be influenced by the intensity of proprioceptive stimulation at the joint.

MAPPIT (MAmmalian Protein-Protein Interaction Trap) as a tool to study HIV reverse transcriptase dimerization in intact human cells.

The high mutation rate of Human Immunodeficiency Virus (HIV) leads to the rapid derivation of compound-resistant virus strains and thus necessitates the identification and development of compounds with alternative mode of actions. MAPPIT (MAmmalian Protein-Protein Interaction Trap) is a highly efficient tool to study protein-protein interactions in intact human cells and is applied to study the dimerization process of the HIV reverse transcriptase complex. Highly specific signals for the p66/p51 and p66/p66 interactions could readily be detected. Specificity was established further by introducing mutations in either subunit. Treatment with efavirenz resulted in an increased MAPPIT signal, with an EC50 value of 64nM for the p66/p51 interaction, and allowed detection of the p51/p51 homodimerization, confirming the context-dependent asymmetric contribution of both subunits. These results show that MAPPIT can be used as a novel screening tool for anti-HIV compounds in intact human cells.

HyperISGylation of Old World monkey ISG15 in human cells.

BACKGROUND: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. PRINCIPAL FINDINGS: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. CONCLUSIONS: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator.